This is a revised competing continuation application for R01 AI055359-02, DOT-HAARTfor HIV-lnfected South African Adults. We are seeking two additional years of funding (5 years total) to complete our trial and attain primary endpoints on all patients. The primary objective of this study is to evaluate the effectiveness and feasibility of directly observed therapy (DOT) using patient-nominated peer supervisors as a strategy to improve adherence to highly active antiretroviral therapy (HAART) in HIV-infected adults in South Africa. Recent international initiatives provide hope for widespread use of HAART in sub-Saharan Africa. However, feasibility, long-term adherence and effective delivery of HAART remain formidable barriers. Peer advocates providing social support and oversight have been used to improve adherence with medical therapies in a variety of settings. We are investigating the utility of Peer-DOT-HAART regimens in South Africa in a randomized trial in which patients are randomized to either Peer-DOT-HAART or self-administration of antiretrovirals for 24 months. The specific aims of this study are: 1) to evaluate the impact of Peer-DOT- HAART on CD4 cell counts and HIV viral load; 2) to evaluate the impact of DOT-HAART on treatment adherence; 3) to determine the frequency of genotypic resistance to HAART during treatment; and 4) to compare incidence of new or recurrent opportunistic infection in both arms. We hypothesize that the patients on the DOT-HAART regimen will have higher levels of treatment adherence and more effective control of viral burden, thereby reducint virologic failure, drug resistance and disease progression. To date, we have enrolled 200 patients into the trial and anticipate reaching full enrollment in late 2006. We will have the preliminary endpoints (1-year viral load and CD4 cell count change) available for all patients in late 2007 and final results in early 2009. This revision provides further details on progress to date and reasons for the delay in starting the trial. This study will generate critical data on an alternative community-based approach of delivering HAART which may become a standard of care applicable throughout sub-Saharan Africa and the whole developing world.